The pathogenic bacterium Helicobacter pylori infects half of the human population and is one of the genetically most diverse bacterial species known. H. pylori was one of the first bacterial species whose genome was sequenced in 1997, and the first species for which two complete sequences from independent isolates were available for within-species comparisons. For almost 10 years, genomic and post-genomic analysis has contributed enormously to our understanding of the pathogenesis of H. pylori infection. This review summarizes the available information, emphasizing work performed in the framework of the PathoGenoMik funding initiative (2001-2006) of the German Ministry of Education and Research.